The long term objective of this proposed research is to contribute to an understanding of how developmental asymmetry is specified in the early embryo. During the course of this fellowship I will identify the mechanisms that regulate asymmetric localization of maternal skn-1 product and activity in the nematode Caenorhabditis elegans. skn-1 encodes a maternally expressed factor that specifies the identity of EMS, one of the lineage founder cells of the early C. elegans embryo. This cell intrinsic factor, designated SKN-1, is differentially localized to the posterior cells of the four cell embryo. Control of maternal skn-1 expression in the embryo will be analyzed by identifying cis-acting sequences within skn-1 RNA and trans-acting factors that regulate SKN-1 localization. Reporter RNAs that reproduce the SKN-1 distribution pattern will be constructed. Sequences within the skn-1 transcript that are responsible for asymmetric localization of skn-1 product will be identified by manipulations of the reporter RNAs. Trans-acting factors that mediate asymmetric distribution of skn-1 product will be identified biochemically, and the genes encoding these regulatory factors will be cloned. Finally, these regulatory factors will be characterized genetically and their functional roles in vivo determined by following skn-1 expression pattern when the factor(s) are absent or ectopically expressed.